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Meiotic DNA replication checkpoint control in fission yeast.
1Cell Cycle Laboratory, Imperial Cancer Research Fund, London WC2A 3PX, UK. murakami@icrf.icnet.uk
Genes & Development
|October 16, 1999
Summary
A DNA replication checkpoint operates during meiosis in fission yeast, requiring specific genes and a protein kinase. This checkpoint prevents premature entry into meiosis I when DNA replication is incomplete, ensuring genomic integrity.
Area of Science:
- Cell Biology
- Genetics
- Molecular Biology
Background:
- Eukaryotic DNA replication checkpoints prevent mitosis entry with incomplete DNA replication, maintaining genomic integrity.
- Equivalent controls during meiosis are less understood.
- Genomic integrity is crucial during both mitosis and meiosis.
Purpose of the Study:
- To investigate the existence and mechanisms of a DNA replication checkpoint during meiosis in fission yeast.
- To identify the key genes and proteins involved in this meiotic checkpoint.
- To understand how this checkpoint regulates the progression of meiosis I.
Main Methods:
- Utilized fission yeast as a model organism.
- Employed genetic analysis involving checkpoint Rad genes and Cds1 protein kinase.
- Monitored Cdc2 tyrosine 15 phosphorylation and Cdc2 protein kinase activity.
- Observed cell cycle progression and arrest states.
Main Results:
- A DNA replication checkpoint operates during meiosis in fission yeast.
- Mitotic checkpoint Rad genes and Cds1 protein kinase are essential for this meiotic checkpoint.
- Cds1 plays a more critical role in the meiotic checkpoint than in mitosis.
- The checkpoint maintains Cdc2 tyrosine 15 phosphorylation, inhibiting Cdc2 kinase activity and preventing meiosis I onset when DNA replication is blocked.
- A second, meiosis-specific checkpoint was identified, leading to cell cycle arrest with high Cdc2 activity and separated spindle pole bodies if Cdc2 phosphorylation is disrupted.
Conclusions:
- Fission yeast possesses a functional DNA replication checkpoint during meiosis.
- This checkpoint utilizes components of the mitotic DNA replication checkpoint machinery.
- A novel, meiosis-specific checkpoint exists, potentially linked to unique meiotic events like recombination and homolog pairing.